A new review published in The BMJ once again opens the question of the risks vs benefits of daily aspirin as a prevention for heart attacks and strokes. The reviewers looked at nine randomized trials involving over 100,000 patients and found that aspirin is effective in reducing heart attacks and strokes, but also increases the risk of gastrointestinal bleeding and that in some patients this risk outweighs the benefit.

This is an old and enduring controversy, and one with significant public health ramifications. Aspirin is an anti-platelet agent – it inhibits platelets, the cell fragments in the blood that are the first line against bleeding, from aggregating (clumping together). Platelets aggregate in order to quickly stop bleeding from damaged veins or arteries. But they can also aggregate around cholesterol plaques in arteries, causing a large thrombus (blood clot) that can block off the artery, or that can break off and lodge in a downstream artery (an embolus) and cause a stroke or heart attack.

By inhibiting platelet aggregation daily aspirin reduces the risk of forming a thrombus or embolus, and thereby reduces the risk of heart attack or stroke. Of course, the real story is always more complex than our straightforward explanations. There is some research to suggest that the anti-inflammatory effects of aspirin may also be important to their role in reducing vascular risk. The relative contribution of anti-platelet and anti-inflammatory effects have not been fully teased out. Further, the anti-inflammatory effects of daily aspirin may have non-vascular benefits, like reducing the risk of some cancers.

By inhibiting the normal function of platelets, however, aspirin also increases the risk of bleeding. Patients taking regular aspirin will often notice that they bruise easily, or bleed for a long time from minor cuts (such as cuts from shaving). In fact these symptoms can be used as a rough guide to how much of an anti-platelet effect an individual patient is getting from their dose of aspirin. Sometimes we will cut back on the dose of aspirin, for example, if patients have excessive bruising. The real concern is not about simple bruising, however, but of significant bleeding. Aspirin can cause or exacerbate gastric ulcers, and if they bleed they will bleed more severely because of the blood-thinning effect of the aspirin. Also, if a patient does have a stroke that stroke is more likely to bleed, and that bleeding is likely to be more severe. Also, patients taking aspirin who suffer trauma are likely to have more severe bleeding from that trauma.

In other words – taking daily aspirin has both risks and benefits. Researchers have for years tried to figure out exactly what the relationship is between aspirin risks and benefit at specific doses of aspirin and in specific populations of people. What is not controversial is that daily aspirin is effective for secondary prevention of heart attacks and strokes. Secondary prevention means (in this case) people who have already had a heart attack or cerebrovascular event (stroke or transient ischemic attack – TIA). There is still some dithering about dose (81mg per day vs 325mg per day), but overall the benefits outweigh the risks.

The enduring controversy is over aspirin for primary prevention, in those who have not already had a vascular event – a heart attack or stroke. The risks of aspirin are generally the same in these two groups. Risk of bleeding complications increases with age, but is not significantly different in the primary vs secondary prevention groups.

What is different is the benefit of aspirin. As a general principle the benefit of any preventive intervention increases as the incidence of the disease or event it is meant to prevent increases. Aspirin has increased benefit for secondary prevention because the population of people who have already had an event are at higher risk of having a subsequent one than those who have never had a vascular event. Heart attacks and strokes are relatively uncommon in people who have never had such an event, and so the benefit of aspirin, while significant as a relative decrease in risk, is very minor as an absolute reduction of risk in the low risk population.

The question is – where do the lines of risk vs benefit cross? This is the question the recent study sought to illuminate.

What they found is that for primary prevention those taking regular aspirin were about 30 percent more likely to have a serious GI bleed. So-called “all-cause mortality” was not different in the aspirin vs no-aspirin groups. Aspirin reduced the risk of heart attacks and strokes (more heart attacks in men and more strokes in women) but less than the increase in GI bleed. For every 162 people taking regular aspirin, one nonfatal heart attack was prevented but there was an increase of about two GI bleeds.

When translated to the general population we are talking about millions of heart attacks, strokes, and bleeds over several years in the US alone, so the public health consequences are huge. In other words, obsessing over small percentage differences has a big effect when translated to the overall population.

This review is not the final word on this question. It leaves us with the same bottom-line conclusion that we had prior to this review (it is a review, so the studies it looked at were already taken into consideration in forming guidelines). That is – for primary prevention aspirin use should be individualized. When looking at the general primary prevention population the risks seem to outweigh the benefits, but perhaps there are subpopulations that are at high risk for a stroke or heart attack in whom aspirin would be a net benefit. It is difficult to study subpopulations for this question because we need very large numbers to get statistically significant results (because the base risk is so low).

But – for those who have diabetes, high blood pressure, high cholesterol, or a strong family history of heart attack or stroke, the benefit of daily aspirin may still outweigh the risks. This means if you were placed on aspirin by your doctor and you have one or more of the above risk factors, this latest study should not make you stop taking aspirin – although you might want to revisit the question with your doctor to see if their recommendations for you have changed.

Official recommendations are to individualize the decision whether or not to use aspirin for primary prevention based upon age, risk of bleeding, and risk factors for vascular disease.

This is a question, with many sub-questions, that was an interesting controversy when I was in medical school two decades ago, has been the subject of ongoing research since then, and researchers continue to refine the data on this question finer and finer. It is an excellent example of evidence-based medicine at work. It is also an example of the real process of individualized medicine -making treatment recommendations based upon the history and risk factors of the individual patient. It further demonstrates the attention and effort that science-based medicine dedicates to preventing disease and morbidity. All of this stands in direct contrast to the propaganda of those who oppose science-based medicine.